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Biomedical subjects

K Carlström

Publications and source records attributed to K Carlström.

At least 55 records · Page 3Linked to original sources

Adrenal responsivity in normal aging and mild to moderate Alzheimer's disease.

BACKGROUND: Enhanced levels of cortisol have been found in moderate to severe Alzheimer's disease (AD) and in major depression, while recent studies have suggested decreased levels of serum dehydroepiandrosterone sulfate (DHAS) in patients with dementia. In this study the responsivity of the adrenal cortex to stimulation with a new low dose adrenocorticotropin (ACTH) test was investigated in patients with AD and in normal aging. METHODS: Thirteen patients with mild to moderate AD, 12 healthy old controls, and 15 young controls (78.0 +/- 8.4, 76.7 +/- 7.0, and 28.3 +/- 4.1 years old, mean: +/- SD, respectively) received an intravenous bolus injection of 1 microgram ACTH. Serum cortisol and androgen levels were analyzed before and 5, 10, 20, 25, 30, 35, 40, 60, 90, 120, 180, and 240 minutes after injection. RESULTS: The cortisol responsivity did not differ between the three groups. An enhanced release of androgens was present in patients with AD. AD per se had an independent influence on androstenedione levels after ACTH stimulation after adjustments for age and gender in a general linear regression model. CONCLUSIONS: In contrast to major depression, increased cortisol release to ACTH stimulation does not seem to be a feature of AD. Abnormal androgen levels after ACTH stimulation are characteristic features of mild to moderate Alzheimer's disease.

Adrenal Cortex Hormones↗

Fibrinolytic factors in endometriotic tissue, endometrium, peritoneal fluid, and plasma from women with endometriosis and in endometrium and peritoneal fluid from healthy women.

OBJECTIVE: To determine whether there is a difference in fibrinolytic compounds in endometriotic tissue, endometrium, peritoneal fluid (PF), and plasma from women with endometriosis and in endometrium and PF from healthy women. DESIGN: Prospective study. SETTING: Two university clinics. PATIENT(S): Regularly menstruating women with and without endometriosis. INTERVENTION(S): Tissue samples, PF, and blood were collected at surgery performed for clinical reasons. MAIN OUTCOME MEASURE(S): The antigen concentrations of plasminogen activators and plasminogen activator inhibitors (PAls) in tissue homogenates, PF, and plasma were assayed by ELISA. RESULT(S): The concentrations of urokinase plasminogen activator (u-PA) and PAI-1 were higher in endometrium from women with endometriosis than in endometrium from controls and even higher in endometriotic tissue than in endometrium from both groups. In PF, the concentration of PAI-2 was higher in women with endometriosis than in controls. CONCLUSION(S): The high concentrations of u-PA and PAI-1 in endometrium from women with endometriosis might facilitate implantation of endometrial cells and the high concentration in endometriotic tissue might contribute to their invasive growth. The inflammatory reaction may contribute to the high concentration of PAI-2.

Adult↗

Insulin-like growth factor-I in women with hydatidiform mole and in normal pregnancy.

OBJECTIVE: To compare molar and placental tissue insulin-like growth factor-I (IGF-I) levels and IGF-I messenger RNA (mRNA) expression and maternal serum IGF-I levels in molar and normal pregnancies of the same gestational length. METHODS: Tissue and serum total IGF-I were measured by radioimmunoassay, and tissue IGF-I mRNA expression was measured by a solution hybridization technique in samples from seven patients with hydatidiform mole in gestational weeks 8 through 14 and from 12 women with normal placentas undergoing induced abortion during weeks 8 through 12. RESULTS: Tissue and serum total IGF-I levels and tissue IGF-I mRNA expression were significantly lower in molar pregnancies than in pregnancies with normal placenta. CONCLUSION: The lower levels of both IGF-I mRNA and of the IGF-I protein itself in hydatidiform mole indicates that the regulation of expression of IGF-I is on the transcriptional level. This finding may reflect a decreased production of the placental growth hormone variant in molar tissue.

Adult↗

Hormonal counterregulation and subjective symptoms during induced hypoglycemia in insulin-dependent diabetes mellitus patients during and after pregnancy.

BACKGROUND: The objective was to elicit whether hormonal responses to and subjective symptoms of hypoglycemia are modified during pregnancy in patients with insulin-dependent diabetes mellitus. METHODS: In ten type I diabetic women, hyperinsulinemic hypoglycemic clamps, with target arterial blood glucose content of 2.2 mmol/l, were performed during the third trimester of pregnancy and 5-13 months after delivery. The levels of arterial glucose and venous catecholamines, pituitary growth hormone, cortisol, glucagon, dehydroepiandrosterone and free insulin were assessed repeatedly. Subjective symptoms of hypoglycemia were recorded on a visual analog scale. The paired t-test and Wilcoxon signed rank test were used for statistical comparisons. RESULTS: Adrenaline and dehydroepiandrosterone increased during hypoglycemia on both occasions, but dehydroepiandrosterone disclosed a significantly different pattern of response during pregnancy (p=0.016). The cortisol increase was augmented during pregnancy (420+/-50 vs. 310+/-30 nmol/l non-pregnant, p=0.039), while the increase in pituitary growth hormone (hGH) was diminished (5.4+/-1.2 vs. 27.9+/-5.4 microg/l non-pregnant, p=0.001), but nevertheless the increase during pregnancy was significant (p=0.002). Three of the eight subjective symptoms of hypoglycemia recorded were less prominent during pregnancy, namely 'inability to concentrate' (p=0.03), 'headache' (p=0.01) and 'pounding heart' (p=0.03). CONCLUSIONS: Albeit some subjective symptoms were diminished during pregnancy, the study gives no evidence that, in diabetic patients, pregnancy per se impairs the counterregulatory response to hypoglycemia, with the exception of growth hormone. However, despite the suppressed basal growth hormone secretion in late pregnancy, the study disclosed a secretory response of this hormone at hypoglycemia.

Adult↗

Exhaled oral and nasal nitric oxide during L-arginine infusion in preeclampsia.

OBJECTIVE: To determine the effects of the nitric oxide (NO) precursor L-arginine on the airway NO concentration in patients with preeclampsia. METHODS: NO was measured by a noninvasive chemiluminescence technique in air sampled directly from nasal and oral cavities during expiration before and during L-arginine infusion in 9 preeclamptic and 10 control pregnancies. Maternal blood pressure and heart rate were simultaneously recorded, and blood was sampled for analyses of cyclic guanosine monophosphate (cGMP) and nitrate. RESULTS: Basal nasal and orally exhaled NO and the increment in nasal NO concentration during L-arginine infusion were similar in both groups. Basal plasma and platelet cGMP concentrations were similar in both groups. Following L-arginine infusion, plasma cGMP levels were significantly higher in preeclamptics (p < 0.01), while platelet cGMP was unaffected in both groups. Basal plasma nitrate was significantly higher in preeclamptics (p < 0.01), and this difference was not altered following infusion. Blood pressure and heart rate remained unaffected by the procedure in both groups. CONCLUSIONS: Blood pressure did not decrease in the preeclamptics following L-arginine infusion, despite a significant increase in nasal NO sampled during breathhold and a concomitant increase in plasma cGMP, possibly reflecting an endogenous NO production. These results do not support the idea of a generalized decrease in NO production being a major cause of hypertension in preeclampsia.

Adult↗

Transurethral microwave thermotherapy in symptomatic benign prostatic hyperplasia: a possible association between androgen status and treatment result?

BACKGROUND: Nothing is yet known of possible endocrine effects of transurethral microwave thermotherapy (TUMT) or of possible influence of endocrine status on the result of thermotherapy. METHODS: Serum levels of testosterone (T), SHBG, estradiol, LH, and PSH were measured in 48 men with BPH before and 2-3 months after TUMT (Prostatron, Prostasoft 2.0; Technomed International, Lyon, France). Assessment of results was based on the patients' own estimations. RESULTS: The treatment did not alter hormone levels. Patients who reported response after 12 months (n = 21) had significantly lower outset levels of calculated free testosterone (fT) than in the nonresponders (n = 27). In the patients aged < 70 years (n = 13), both the fT and T values were lower than in the nonresponders (n = 15). There was no age difference between responders and nonresponders. CONCLUSIONS: TUMT did not influence hormone levels. These observations suggest that androgen status may influence the final result of treatment.

Aged↗

Possible bone-preserving capacity of high-dose intramuscular depot estrogen as compared to orchidectomy in the treatment of patients with prostatic carcinoma.

BACKGROUND: Treatment of prostatic disease with GnRH agonists or by orchidectomy affects bone mass negatively. Estrogen treatment has beneficial effects on bone mass in women and might hypothetically have a bone preserving capacity also in patients with prostatic cancer. METHODS: We followed serum markers for bone and collagen metabolism and sex steroids for 18 months in patients with prostatic cancer treated by orchidectomy (N = 13) or by single-drug parenteral polyestradiol phosphate (240 mg intramuscularly every second week for the first two months, and then every fourth week; N = 17). RESULTS: Total and free testosterone reached castration levels within 1.5 months of estrogen treatment. Four patients developing progressive disease and/or signs of metastasis were excluded from the analysis. In the remaining patients, serum osteocalcin, procollagen IIIP (PIIINP), procollagen (PICP), and the crosslinked carboxyterminal telopeptide of type I collagen (ICTP) increased significantly over time following orchidectomy (N = 11). Serum osteocalcin and PICP decreased significantly over time during estrogen treatment (N = 15). Treatment values of all four markers were significantly lower in estrogen-treated than in orchidectomized patients. CONCLUSIONS: The changes in serum bone and collagen markers indicate an increased bone turnover in orchidectomized subjects. The opposite pattern was found in the estrogen-treated patients, indicating a reduced turnover. Estrogens may also have a bone mass-preserving capacity in elderly males with prostatic cancer.

Aged↗

Use of a hormone-sensitive (LNCaP) and a hormone-resistant (LNCaP-r) cell line in prostate cancer research.

BACKGROUND: In order to develop a hormone-resistant analog to the hormone sensitive cell-line LNCaP, different methods were tried. METHODS: After almost one year of continuous culture in RPMI-1640, containing a low concentration of androgens, the hormone sensitive cell-line LNCaP became hormone resistant and was named LNCaP-r. RESULTS: We used the LNCaP/LNCaP-r model system in order to study methods for the parenteral treatment of prostate carcinoma with estrogens, to study the mechanism of action of estramustine, and to identify markers useful as predictive tests for prostate carcinoma. CONCLUSIONS: A model system made up of the hormone sensitive prostate LNCaP cell-line and the hormone resistant LNCaP-r subline was developed and characterized. This system is, despite a number of limitations, easy to use as a first step to test different hypotheses that can be studied further in later clinical trials.

Androgens↗

Proliferation of breast epithelial cells in healthy women during the menstrual cycle.

OBJECTIVE: Our objective was to assess proliferation in normal breast epithelial cells from healthy women during the follicular and luteal phases of the menstrual cycle. STUDY DESIGN: We analyzed the proliferation marker Ki-67/MIB-1 by immunocytochemical methods in breast epithelial cells procured through fine needle aspiration biopsy from 47 healthy volunteers. Differences were assessed by Wilcoxon rank sum tests, and correlations were determined by Spearman's rank correlation coefficient. RESULTS: The proportion of KI-67/MIB-1-positive cells was higher in the luteal phase (2.04%) than in the follicular phase (1.66%). The values in women aged < 35 years were 2.29% and 1.13%, respectively (p = 0.003). In ovulating women with two aspirates during the same menstrual cycle the percentage of proliferating cells increased from the follicular phase (1.3%) to the luteal phase (2.4%) (p < 0.04). Proliferation was positively correlated with serum progesterone levels the day of aspiration (r = 0.34, p < 0.05). CONCLUSION: The fine needle aspiration biopsy technique is a valuable tool for in vivo studies of cell proliferation in the normal breast. Data clearly suggest a proliferative action of progesterone.

Adolescent↗

Testicular and adrenocortical function in men with prostatic cancer and in healthy age-matched controls.

OBJECTIVE: To compare the endocrine status of patients with prostate cancer with that of age-matched healthy controls. PATIENTS, SUBJECTS AND METHODS: Basal serum concentrations of sex steroids, sex hormone-binding globulin (SHBG) and gonadotrophins, and the basal levels and response to adreno-corticotropic hormone (ACTH) of adrenocortical steroids, were measured before treatment in 72 patients with prostate cancer and in 42 age-matched healthy controls. RESULTS: Patients aged < 60 years with prostate cancer had significantly elevated levels of total testosterone and unconjugated (E1) and total (tE1) oestrone while patients aged > or = 60 years had significantly elevated levels of total and non-SHBG-bound testosterone (NST). 17 alpha-hydroxyprogesterone and tE1. Gonadotrophins, SHBG levels and relationships between total testosterone and SHBG were normal in both age groups of patients, as were basal levels and ACTH-induced increments of adrenocortical steroids. The patients had normal age-related variations in SHBG and NST and in basal levels and ACTH-induced increments of adrenocortical steroids. There was a significant age-related increase in serum E1 in the control subjects but not in the patients. Patients with metastatic disease had significantly lower tE1 levels than had patients without metastases. CONCLUSIONS: The results suggest an increased sensitivity of the testis to gonadotrophic stimulation, as well as an increased peripheral oestrogen synthesis in patients with prostate cancer, the latter being most pronounced in younger subjects. Men developing prostate cancer may have been exposed to a combination of elevated endogenous oestrogen and androgen levels for a long time. These findings support the theory of a synergism between oestrogens and androgens as an important factor in the aetiology of prostate cancer.

17-alpha-Hydroxyprogesterone↗

Preoperative infiltration of bupivacaine--effects on pain relief and trauma response (cortisol and interleukin-6).

HYPOTHESIS: Subcutaneous infiltration of bupivacaine before skin incision can reduce postoperative pain and modulate the stress response. METHODS: In a randomized study on pain relief after hysterectomy 29 patients were referred into one of three groups, receiving 30 ml of bupivacaine 0.25% with adrenaline, 30 ml of saline or no infiltration along the line of the proposed incision 10 min before start of surgery. A Visual Analogue Scale was used for repeated pain ratings. Postoperative pain relief was provided with patient-controlled analgesia with intravenous morphine 0.04 mg/kg. Lockout time was 10 min. The immunological and endocrine stress response to trauma was reflected by blood interleukin-6 (IL-6) and cortisol concentrations measured during 72 h following skin incision. RESULTS: There were large individual variations in the accumulated postoperative consumption of morphine at 20 h after start of surgery. It was significantly reduced in patients receiving infiltration of bupivacaine. They used 39 mg (9-62) median (range) of intravenous morphine whereas the patients in the saline group used 65 mg (47-120) and patients in the control group used 54 mg (36-130) (P < 0.05). Significant elevation of plasma IL-6 and serum cortisol levels appeared in all groups with peak values at 3 h. There were no differences between the groups. There was a correlation between cortisol and IL-6. Six of the 29 patients had a postoperative infection which was reflected in increased IL-6 levels. CONCLUSION: Preoperative subcutaneous infiltration of bupivacaine significantly reduced the postoperative consumption of intravenous morphine.

Adult↗

Hormonal patterns in postmenopausal women during gynecological surgery.

The endocrine effects of surgical trauma are incompletely understood. We have measured serum levels of cortisol, 17 alpha-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHA), 4-androstene-3,17-dione (A4) and total (free + conjugated) estrone (tE1) before, during and up to 6 days after surgery in 30 postmenopausal women undergoing repair of vaginal prolapse. Anesthetic procedures were standardized. During surgery and the early postoperative hours the serum steroid pattern closely resembled that found during a diagnostic ACTH challenge test with a simultaneous increase in all adrenocortical steroids, while tE1 levels were unchanged. During the late postoperative period the levels of cortisol, 17-OHP and A4 were still elevated up to 24 h after surgery while the levels of DHA were normal or even decreased. The postoperative pattern of adrenocortical steroids may reflect a redistribution of the intra-adrenal steroid flux in favor of cortisol production. The tE1 levels were elevated in the early and, most pronounced, in the late postoperative phase. tE1 was positively correlated to A4, in the early but not in the late postoperative phase. The late increase in tE1 probably reflects an impaired bowel function in connection with surgery, leading to increased reabsorption during enterohepatic circulation.

17-alpha-Hydroxyprogesterone↗

Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance?

The polycystic ovary syndrome (PCOS) is the most common hyperandrogenic disorder among women and is characterized by metabolic and cardiovascular aberrations similar to those seen in the so-called insulin resistance syndrome. The regulation of lipolysis was investigated in isolated abdominal sc adipocytes from 10 nonobese women with PCOS and in 11 age- and body mass index-matched healthy women. Eight PCOS women were reinvestigated after 3 months of treatment with combined oral contraceptives containing ethinyl estradiol and norethisterone, which normalized hyperandrogenicity. The PCOS women showed a marked resistance to the lipolytic effect of noradrenaline due to defects at two different levels in the lipolytic cascade: first, a 7-fold reduction in sensitivity to the beta 2-selective agonist terbutaline (P < 0.005), which could be ascribed to a 50% lower beta 2-adrenoceptor density (P < 0.02) as determined with radioligand binding; there was no difference with regard to dobutamine (beta 1) or clonidine (alpha 2-sensitivity) or beta 1-adrenoceptor density; second, the maximum lipolytic response was also 35% lower (P < 0.02) in the PCOS women compared to that in the healthy women. This was seen with all beta-adrenergic agonists and the postreceptor-acting agents forskolin (activating adenylyl cyclase) and dibutyryl cAMP (activating protein kinase). Neither beta 2-adrenoceptor sensitivity or density nor the reduced lipolytic responsiveness was restored by 3 months of oral contraceptives treatment. The results indicate the existence of a marked impairment of catecholamine-induced lipolysis in nonobese PCOS women displaying early features of the insulin resistance syndrome due to multiple lipolysis defects as a lower beta 2-adrenoceptor density and reduced function of the protein kinase, hormone-sensitive lipase complex. These lipolysis defects are identical to those observed in the insulin resistance (metabolic) syndrome and could be a primary pathogenic mechanism for the development of these disorders.

Adipocytes↗

Endothelin-1 and big endothelin-1 levels in normal term pregnancy and in preeclampsia.

To study the concentrations of endothelin-1 (ET-1) and its precursor, big ET-1, in samples of amniotic fluid, fetal urine, umbilical arterial and venous blood, retroplacental blood and maternal uterine and brachial venous blood obtained from normal and preeclamptic women. Samples were collected from 31 healthy pregnant women (16 in labor and 15 undergoing elective cesarean section) and 35 preeclamptic women (9 in labor and 26 undergoing cesarean section). Big ET-1 and ET-1 were measured by radioimmunoassay and the ET-1 to big ET-1 ratios were calculated. In preeclamptic women there was a significant elevation of ET-1 in the maternal brachial and uterine veins and of big-ET-1 in the brachial vein. The ET-1 concentrations and the ET-1/big ET ratios were significantly higher on the fetal side (i.e., in the umbilical vein and amniotic fluid) than in maternal blood, but in these sampling locations there was no difference between the normal pregnancy and preeclampsia group. A significant negative correlation (r = -0.67, P < 0.01) was found between plasma ET-1 in the umbilical vein and birth weight in the preeclamptic group. ET-1 was significantly higher in amniotic fluid than in the first neonatal urine of corresponding pregnancies (15.0 +/- 2.0 vs. 3.0 +/- 2.9 pmol/l, P < 0.05). The ET-1 and big ET-1 concentrations are significantly higher in fetal plasma and amniotic fluid than in maternal plasma, indicating increased endothelin converting enzyme activity and increased ET-1 production in utero. The elevated ET-1 concentration in maternal blood in preeclamptic compared with normal pregnant women and the negative correlation between ET-1 in the umbilical vein and birth weight suggest that ET-1 plays a pathophysiological role in preeclampsia and other conditions with intrauterine growth restriction.

Adult↗

Blunted adrenocorticotropin and increased adrenal steroid response to human corticotropin-releasing hormone in Alzheimer's disease.

Previous studies suggest disturbances in the central regulation of the hypothalamic-pituitary-adrenocortical axis (HPA) in advanced Alzheimer's disease (AD). In this study the reactivity of the HPA axis was evaluated by stimulation with corticotropin-releasing hormone (CRH) of patients with mild to moderate AD. Twenty-three patients with AD (aged 61-88 yr) and 19 healthy elderly (aged 62-84 yr) received an intravenous bolus injection of human CRH (1 microgram/kg) at 3:00 PM. CRH-stimulated plasma ACTH levels were significantly lower in AD patients, while serum cortisol, dehydroepiandrosterone, and androstenedione responses relative to the amount of ACTH released were higher in AD patients. Significant correlations were found between low basal plasma ACTH levels and temporal lobe atrophy (p=0.02) and between peak plasma ACTH levels and hippocampal atrophy (p = 0.01). These findings suggest abnormalities at several levels of HPA axis in AD.

Adrenocorticotropic Hormone↗